The overall objective of this research effort is to elucidate the cellular and molecular mechanisms involved in the regulation of immune responses to orally-administered Streptococcus mutans. In vivo studies in rodents are establishing the precise nature of an oral vaccine most effective in inducing a protective salivary antibody response to S. mutans. The information gained from these studies is being tested in human volunteers in order to obtain additional evidence for the existence of a common mucosal immune system and to determine the effectiveness of the oral vaccine for inducing salivary responses which reduce the level of S. mutans in plaque and subsequent dental caries. Molecular adjuvants are also being incorporated into the oral vaccines in order to potentiate immune responses. In vitro studies are aimed toward understanding the cellular basis of induction and enhancement of IgA immune responses to S. mutans, including the role of macrophages and T and B cells and their soluble mediators in these responses. These studies are being performed in murine, rat and human systems. These studies will allow us to determine the form and nature of the S. mutans antigen(s) which will be efficacious and effective for use as a human oral vaccine.